Method of treating cancer using FPT inhibitors and antineoplastic agents

Abstract

Disclosed is a method of treating cancer in a patient in need of such treatment comprising administering a therapeutically effective amount of an FPT inhibitor and therapeutically effective amounts of one or more antineoplastic agents. Methods of treating non small cell lung cancer, squamous cell cancer of the head and neck, CML, AML, non-Hodgkin's lymphoma and multiple myeloma are disclosed.

What is claimed is  
     
         1 . A method of treating cancer comprising administering to a patient in need of such treatment therapeutically effective amounts of: 
 (a) an FPT inhibitor of formula 1.0; and    (b) at least two different antineoplastic agents selected from the group consisting of: 
 (1) taxanes;  
 (2) platinum coordinator compounds;  
 (3) EGF inhibitors that are antibodies;  
 (4) EGF inhibitors that are small molecules;  
 (5) VEGF inhibitors that are antibodies;  
 (6) VEGF kinase inhibitors that are small molecules;  
 (7) estrogen receptor antagonists or selective estrogen receptor modulators;  
 (8) anti-tumor nucleoside derivatives;  
 (9) epothilones;  
 (10) topoisomerase inhibitors;  
 (11) vinca alkaloids;  
 (12) antibodies that are inhibitors of αVβ3 integrins;  
 (13) small molecule inhibitors of αVβ3 integrins;  
 (14) folate antagonists;  
 (15) ribonucleotide reductase inhibitors;  
 (16) anthracyclines;  
 (17) biologics;  
 (18) Thalidomide (or related Imid); and  
 (19) Gleevec;  
   wherein said FPT inhibitor is a compound of the formula:                          or a pharmaceutically acceptable salt or solvate thereof, wherein:    one of a, b, c and d represents N or N + O − , and the remaining a, b, c, and d groups represent carbon, wherein each carbon has an R 1  or R 2  group bound to said carbon; or    each of a, b, c, and d is carbon, wherein each carbon has an R 1  or R 2  group bound to said carbon;    the dotted lines (—) represent optional bonds;    X represents N or CH when the optional bond is absent, and represents C when the optional bond is present;    when the optional bond is present between carbon atom 5 and carbon atom 6 then there is only one A substituent bound to carbon atom 5 and there is only one B substituent bound to carbon atom 6 and A or B is other than H;    when the optional bond is not present between carbon atom 5 and carbon atom 6, then there are two A substituents bound to carbon atom 5 and two B substituents bound to carbon atom 6, wherein each A and B substituent is independently selected from the group consisting of: 
 (1) —H;  
 (2) —R 9 ;  
 (3) —R 9 —C(O)—R 9 ;  
 (4) —R 9 —CO 2 —R 9a ;  
 (5) —(CH 2 )pR 26 ;  
 (6) —C(O)N(R 9 ) 2 , wherein each R 9  is the same or different;  
 (7) —C(O)NHR 9 ;  
 (8) —C(O)NH—CH 2 —C(O)—NH 2 ;  
 (9) —C(O)NHR 26 ;  
 (10) —(CH 2 )pC(R 9 )—O—R 9a ;  
 (11) —(CH 2 )p(R 9 ) 2 , wherein each R 9  is the same or different;  
 (12) —(CH 2 )pC(O)R 9 ;  
 (13) —(CH 2 )pC(O)R 27a ;  
 (14) —(CH 2 )pC(O)N(R 9 ) 2 , wherein each R 9  is the same or different;  
 (15) —(CH 2 )pC(O)NH(R 9 );  
 (16) —(CH 2 )pC(O)N(R 26 ) 2 , wherein each R 26  is the same or different;  
 (17) —(CH 2 )pN(R 9 )—R 9a ;  
 (18) —(CH 2 )pN(R 26 ) 2 , wherein R 26  is the same or different;  
 (19) —(CH 2 )pNHC(O)R 50 ;  
 (20) —(CH 2 )pNHC(O) 2 R 50 ;  
 (21) —(CH 2 )pN(C(O)R 27a ) 2  wherein each R 27a  is the same or different;  
 (22) —(CH 2 )pNR 51 C(O)R 27 , or R 51  and R 27  taken together with the atoms to which they are bound form a heterocycloalkyl ring consisting of, 5 or 6 members, provided that when R 51  and R 27  form a ring, R 51  is not H;  
 (23) —(CH 2 )pNR 51 C(O)NR 27 , or R 51  and R 27  taken together with the atoms to which they are bound form a heterocycloalkyl ring consisting or 5 or 6 members, provided that when R 51  and R 27  form a ring, R 51  is not H;  
 (24) —(CH 2 )pNR 51 C(O)N(R 27a ) 2 , wherein each R 27a  is the same or different;  
 (25) —(CH 2 )pNHSO 2 N(R 51 ) 2 , wherein each R 51  is the same or different;  
 (26) —(CH 2 )pNHCO 2 R 50 ;  
 (27) —(CH 2 )pNC(O)NHR 51 ;  
 (28) —(CH 2 )pCO 2 R 51 ;  
 (29) —NHR 9 ;  
 (30)  
                     
 wherein  
   R 30  and R 31  are the same or different; 
 (31)  
                     
 wherein  
   R 30 , R 31 , R 32  and R 33  are the same or different; 
 (32) -alkenyl-CO 2 R 9a ;  
 (33) -alkenyl-C(O)R 9a ;  
 (34) -alkenyl-CO 2 R 51 ;  
 (35) -alkenyl-C(O)—R 27a ;  
 (36) (CH 2 )p-alkenyl-CO 2 —R 51 ;  
 (37) —(CH 2 )pC═NOR 51  and  
 (38) —(CH 2 )p-Phthalimid;  
   p is 0, 1, 2, 3 or 4;    each R 1  and R 2  is independently selected from H, Halogen, —CF 3 , —OR 10 , COR 10 , —SR 10 , —S(O) t   15  wherein t is 0, 1 or 2, —N(R 10 ) 2 , —NO 2 , —OC(O)R 10 , CO 2 R 10 , —OCO 2 R 15 , —CN, —NR 10 COOR 15 , —SR 15 C(O)OR 15  —SR 15 N(R 13 ) 2  provided that R 15  in —SR 15 N(R 13 ) 2  is not —CH 2 , and wherein each R 13  is independently selected from H or —C(O)OR 15 , benzotriazol-1-yloxy, tetrazol-5-ylthio, or substituted tetrazol-5-ylthio, alkynyl, alkenyl or alkyl, said alkyl or alkenyl group optionally being substituted with halogen, —OR 10  or —CO 2 R 10 ;    R 3  and R 4  are the same or different and each independently represent H, or any of the substituents of R 1  and R 2 ;    R 5 , R 6 , R7 and R 7a  each independently represent H, —CF 3 , —COR 10 , alkyl or aryl, said alkyl or aryl optionally being substituted with —OR 10 , —SR 10 , —S(O) t R 15 , —NR 10 COOR 15 , —N(R 10 ) 2 , —NO 2 , —C(O)R 10 , —OCOR 10 , —OCO 2 R 15 , —CO 2 R 10 , OPO 3 R 10 , or R 5  is combined with R 6  to represent ═O or ═S;    R 8  is selected from the group consisting of:                          R 9  is selected from the group consisting of: 
 (1) heteroaryl;  
 (2) substituted heteroaryl;  
 (3) arylalkoxy;  
 (4) substituted arylalkoxy;  
 (5) heterocycloalkyl;  
 (6) substituted heterocycloalkyl;  
 (7) heterocycloalkylalkyl;  
 (8) substituted heterocycloalkylalkyl;  
 (9) heteroarylalkyl;  
 (10) substituted heteroarylalkyl;  
 (11) heteroarylalkenyl;  
 (12) substituted heteroarylalkenyl;  
 (13) heteroarylalkynyl;  
 (14) substituted heteroarylalkynyl;  
 (15) arylalkyl;  
 (16) substituted arylalkyl;  
 (17) alkenyl, and  
 (18) substituted alkenyl;  
   wherein said substituted R 9  groups are substituted with one or more substituents selected from the group consisting of: 
 (1) —OH;  
 (2) —CO 2 R 14 ;  
 (3) —CH 2 OR 14 ,  
 (4) halogen;  
 (5) alkyl;  
 (6) amino;  
 (7) trityl;  
 (8) heterocycloalkyl;  
 (9) cycloalkyl;  
 (10) arylalkyl;  
 (11) heteroaryl;  
 (12) heteroarylalkyl and  
 (13)  
                     
 wherein  
   R 14  is independently selected from the group consisting of: H; alkyl; aryl, arylalkyl, heteroaryl and heteroarylalkyl;    R 9a  is selected from the group consisting of: alky and arylalkyl;    R 10  is selected from the group consisting of: H; alkyl; aryl and arylalkyl;    R 11  is selected from the group consisting of: 
 (1) alkyl;  
 (2) substituted alkyl;  
 (3) aryl;  
 (4) substituted aryl;  
 (5) cycloalkyl;  
 (6) substituted cycloalkyl;  
 (7) heteroaryl;  
 (8) substituted heteroaryl;  
 (9) heterocycloalkyl; and  
 (10) substituted heterocycloalkyl;  
   wherein said substituted R 11  groups have 1, 2 or 3 substituents selected from the group consisting of: 
 (1) —OH;  
 (2) halogen and  
 (3) alkyl;  
   R 11a  is selected from the group consisting of: 
 (1) H;  
 (2) OH;  
 (3) alkyl;  
 (4) substituted alkyl;  
 (5) aryl;  
 (6) substituted aryl;  
 (7) cycloalkyl;  
 (8) substituted cycloalkyl;  
 (9) heteroaryl;  
 (10) substituted heteroaryl;  
 (11) heterocycloalkyl; and  
 (12) substituted heterocycloalkyl;  
   wherein said substituted R 11a  groups have one or more substituents selected from the group consisting of: 
 (1) —OH;  
 (2) —CN;  
 (3) —CF 3 ;  
 (4) halogen;  
 (5) alkyl;  
 (6) cycloalkyl;  
 (7) heterocycloalkyl,  
 (8) arylalkyl;  
 (9) heteroarylalkyl;  
 (10) alkenyl and  
 (11) heteroalkenyl;  
   R 12  is selected from the group consisting of: H, and alkyl;    R 15  is selected from the group consisting of: alkyl and aryl;    R 21 , R 22  and R 46  are independently selected from the group consisting of: 
 (1) —H;  
 (2) alkyl;  
 (3) aryl;  
 (4) substituted aryl, 
 optionally substituted with one or more substituents selected from the group consisting of: alkyl, halogen, CF 3  and OH;  
 
 (5) cycloalkyl;  
 (6) substituted cycloalkyl; 
 optionally substituted with one or more substituents selected from the group consisting of: alkyl, halogen, CF 3  and OH;  
 
 (7) heteroaryl of the formula,  
                     
 (8) heterocycloalkyl of the formula:  
                     
 wherein  
   R 44  is selected from the group consisting of: 
 (1) —H;  
 (2) alkyl;  
 (3) alkylcarbonyl;  
 (4) alkyloxy carbonyl;  
 (5) haloalkyl and  
 (6) —C(O)NH(R 51 );  
   when R 21 , R 22  or R 46  is the heterocycloalkyl of the formula above, Ring V is selected from the group consisting of:                          R 26  is selected from the group consisting of: 
 (1) —H;  
 (2) alkyl;  
 (3) alkoxyl;  
 (4) —CH 2 —CN;  
 (5) R 9 ;  
 (6) —CH 2 CO 2 H;  
 (7) —C(O)alkyl and  
 (8) CH 2 CO 2 alkyl;  
   R 27  is selected from the group consisting of: 
 (1) —H;  
 (2) —OH;  
 (3) alkyl and  
 (4) alkoxy;  
   R 27a  is selected from the group consisting of: 
 (1) alkyl and  
 (2) alkoxy;  
   R 30  through R 33  are independently selected from the group consisting of: 
 (1) —H;  
 (2) —OH;  
 (3) ═O;  
 (4) alkyl;  
 (5) aryl and  
 (6) arylalkyl;  
   R 50  is selected from the group consisting of: 
 (1) alkyl;  
 (2) heteroaryl;  
 (3) substituted heteroaryl and  
 (4) amino;  
   wherein said substituents on said substituted R 50  groups are independently selected from the group consisting of: alkyl; halogen; and —OH;    R 50a  is selected from the group consisting of: 
 (1) heteroaryl;  
 (2) substituted heteroaryl and  
 (3) amino;  
   R 51  is selected from the group consisting of: —H, and alkyl.    
     
     
         2 . The method of  claim 1  wherein two antineoplastic agents are used wherein one antineoplastic agent is a taxane, and the other antineoplastic agent is a platinum coordinator compound.  
     
     
         3 . The method of  claim 2  wherein said taxane is selected from Paclitaxel or Docetaxel, and said platinum coordinator compound is selected from carboplatin or cisplatin.  
     
     
         4 . The method of  claim 2  wherein said taxane is Paclitaxel and said platinum coordinator compound is Carboplatin.  
     
     
         5 . The method of  claim 2  wherein said taxane is Paclitaxel and said platinum coordinator compound is Cisplatin.  
     
     
         6 . The method of  claim 2  wherein said taxane is Docetaxel and said platinum coordinator compound is Cisplatin.  
     
     
         7 . The method of  claim 2  wherein said taxane is docetaxel and said platinum coordinator compound is Carboplatin.  
     
     
         8 . The method of  claim 2  wherein: said taxane is Paclitaxel administered in an amount of about 150 mg to about 300 mg/m 2  once every three weeks per cycle, and said platinum coordinator compound is Carboplatin administered once every three weeks per cycle in amount of to provide an AUC of about 5 to about 8.  
     
     
         9 . The method of  claim 2  wherein: said taxane is Docetaxel administered in an amount of about 50 mg to about 100 mg/m 2  once every three weeks per cycle, and said platinum coordinator compound is Cisplatin administered in amount of about 60 mg to about 100 mg/m 2  once every three weeks per cycle.  
     
     
         10 . The method of  claim 2  wherein said FPT inhibitor is administered in an amount of about 50 mg to about 200 mg twice a day.  
     
     
         11 . The method of  claim 10  wherein said FPT inhibitor is administered in an amount of about 75 mg to about 125 mg twice a day.  
     
     
         12 . The method of  claim 2  wherein the treatment is given for one to four weeks per cycle.  
     
     
         13 . The method of  claim 2  wherein non small cell lung cancer is treated.  
     
     
         14 . The method of  claim 1  wherein two antineoplastic agents are used wherein one antineoplastic agent is a taxane, and the other antineoplastic agent is an EGF inhibitor that is an antibody.  
     
     
         15 . The method of  claim 14  wherein said taxane is Paclitaxel and said EGF inhibitor is Herceptin.  
     
     
         16 . The method of  claim 1  wherein two antineoplastic agents are used and wherein one antineoplastic agent is an antinucleoside derivative, and the other antineoplastic agent is a platinum coordinator compound.  
     
     
         17 . The method of  claim 16  wherein said antinucleoside derivative is Gemcitabine and said platinum coordinator compound is Cisplatin.  
     
     
         18 . The method of  claim 16  wherein said antinucleoside derivative is Gemcitabine and said platinum coordinator compound is Carboplatin.  
     
     
         19 . The method of  claim 1  wherein non small cell lung cancer is being treated in a patient in need of such treatment comprising administering therapeutically effective amounts of: 
 (a) the FPT inhibitor of formula 1.0; and  
 (b) Carboplatin; and  
 (c) Paclitaxel.  
 
     
     
         20 . The method of  claim 19  wherein said FPT inhibitor is administered twice a day, said Carboplatin is administered once every three weeks per cycle, and said Paclitaxel is administered once every three weeks per cycle, said treatment being given for one to four weeks per cycle.  
     
     
         21 . The method of  claim 20  wherein said FPT inhibitor is administered in an amount of about 50 mg to about 200 mg twice a day, said Carboplatin is administered once every three weeks per cycle in an amount to provide an AUC of about 5 to about 8, said Paclitaxel is administered once every three weeks per cycle in an amount of about 150 to about 300 mg/m 2 , and wherein said carboplatin and said Paclitaxel are administered on the same day.  
     
     
         22 . The method of  claim 21  wherein said FPT inhibitor is administered in an amount of about 75 mg to about 125 mg twice a day.  
     
     
         23 . The method of  claim 22  wherein said FPT inhibitor is administered in an amount of about 100 mg twice a day.  
     
     
         24 . The method of  claim 1  wherein non small cell lung cancer is being treated in a patient in need of such treatment comprising administering therapeutically effective amounts of: 
 (a) the FPT inhibitor of formula 1.0; and:  
 (b) Cisplatin; and  
 (c) Gemcitabine.  
 
     
     
         25 . The method of  claim 24  wherein said FPT inhibitor is administered twice a day, said cisplatin is administered once every three or four weeks per cycle, and said gemcitabine is administered once a week per cycle, said treatment being given for one to seven weeks per cycle.  
     
     
         26 . The method of  claim 25  wherein said FPT inhibitor is administered in an amount of about 50 mg to about 200 mg twice a day, said Cisplatin is administered once every three or four weeks per cycle in an amount of about 60 to about 100 mg/m 2 , and said Gemcitabine is administered once a week per cycle in an amount of about 750 to about 1250 mg/m 2 .  
     
     
         27 . The method of  claim 26  wherein said FPT inhibitor is administered in an amount of about 75 mg to about 125 mg twice a day.  
     
     
         28 . The method of  claim 27  wherein said FPT inhibitor is administered in an amount of about 100 mg twice a day.  
     
     
         29 . The method of  claim 1  wherein non small cell lung cancer is being treated in a patient in need of such treatment comprising administering therapeutically effective amounts of: 
 (a) the FPT inhibitor of formula 1.0; and  
 (b) Carboplatin; and  
 (c) Gemcitabine.  
 
     
     
         30 . The method of  claim 29  wherein said FPT inhibitor is administered twice a day, said Carboplatin is administered once every three weeks per cycle, and said gemcitabine is administered once a week per cycle, said treatment being given for one to seven weeks per cycle.  
     
     
         31 . The method of  claim 30  wherein said FPT inhibitor is administered in an amount of about 50 mg to about 200 mg twice a day, said Carboplatin is administered once every three weeks per cycle in an amount to provide an AUC of about 5 to about 8, and said Gemcitabine is administered once a week per cycle in an amount of about 750 to about 1250 mg/m 2 .  
     
     
         32 . The method of  claim 31  wherein said FPT inhibitor is administered in an amount of about 75 mg to about 125 mg twice a day.  
     
     
         33 . The method of  claim 32  wherein said FPT inhibitor is administered in an amount of about 100 mg twice a day.  
     
     
         34 . The method of  claim 1  comprising administering therapeutically effective amounts of: 
 (a) the FPT inhibitor of formula 1.0; and  
 (b) an antineoplastic agent selected from the group consisting of: 
 (1) EGF inhibitors that are antibodies;  
 (2) EGF inhibitors that are small molecules;  
 (3) VEGF inhibitors that are antibodies; and  
 (4) VEGF kinase inhibitors that are small molecules.  
 
 
     
     
         35 . The method of  claim 34  wherein said antineoplastic agent is selected from the group consisting of: Herceptin, Cetuximab, Tarceva, Iressa, Bevacizumab, IMC-1C11, SU5416, and SU6688.  
     
     
         36 . The method of  claim 35  wherein said FPT inhibitor is administered twice a day, said antineoplastic agent that is an antibody is administered once a week per cycle and said antineoplastic agent that is a small molecule is administered daily, said treatment being given for one to four weeks per cycle.  
     
     
         37 . The method of  claim 36  wherein said FPT inhibitor is administered in an amount of about 50 mg to about 200 mg twice a day, and said antineoplastic agent that is an antibody is administered once a week per cycle in an amount of about 2 to about 10 mg/m 2 , and said antineoplastic agent that is a small molecule is administered in an amount of about 50 to about 2400 mg/m 2 .  
     
     
         38 . The method of  claim 37  wherein said FPT inhibitor is administered in an amount of about 75 mg to about 125 mg twice a day.  
     
     
         39 . The method of  claim 38  wherein said FPT inhibitor is administered in an amount of about 100 mg twice a day.  
     
     
         40 . The method of  claim 2  wherein: said taxane is Paclitaxel administered in an amount of about 150 mg to about 300 mg/m 2  once a week per cycle, and said platinum coordinator compound is Carboplatin administered once a week per cycle in an amount to provide an AUC of about 5 to about 8.  
     
     
         41 . The method of  claim 2  wherein: said taxane is Docetaxel administered in an amount of about 50 mg to about 100 mg/m 2  once a week per cycle, and said platinum coordinator compound is Cisplatin administered in amount of about 60 mg to about 100 mg/m 2  once a week per cycle.  
     
     
         42 . The method of  claim 1  wherein said FPT inhibitor of formula 1.0 is selected from any one of the Examples 1-505.  
     
     
         43 . The method of  claim 34  wherein said FPT inhibitor of formula 1.0 is selected from any one of the Examples 1-505.  
     
     
         44 . The method of  claim 1  wherein said FPT inhibitor of formula 1.0 is selected from the group consisting of:  
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         45 . The method of  claim 1  wherein said FPT inhibitor of formula 1.0 is selected from the group consisting of:  
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         46 . The method of  claim 1  wherein the cancer being treated is CML and the antneoplastic agents are Gleevec and Interferon.  
     
     
         47 . The method of  claim 1  wherein the cancer being treated is CML and the antneoplastic agents are Gleevec and Pegylated interferon.  
     
     
         48 . The method of  claim 1  wherein the cancer being treated is AML and said treatment comprises the administration of therapeutically effective amounts of: 
 (a) the FPT inhibitor of formula 1.0; and  
 (b) an anti-tumor nucleoside derivative.  
 
     
     
         49 . The method of  claim 48  wherein said antinucleoside derivative is Cytarabine.  
     
     
         50 . The method of  claim 48  further comprising the administration of a therapeutically effective amount of anthracycline.  
     
     
         51 . The method of  claim 49  further comprising the administration of a therapeutically effective amount of anthracycline.  
     
     
         52 . The method of  claim 1  wherein said cancer being treated is non-Hodgkin's lymphoma and said treatment comprises the administration of therapeutically effective amounts of: 
 (a) the FPT inhibitor of formula 1.0; and  
 (b) Rituximab.  
 
     
     
         53 . The method of  claim 52  further comprising the administration of a therapeutically effective amount of an anti-tumor nucleoside derivative.  
     
     
         54 . The method of  claim 53  wherein said anti-tumor nucleoside derivative is Fludarabine.  
     
     
         55 . The method of  claim 1  wherein said cancer being treated is non-Hodgkin's lymphoma and said treatment comprises the administration of therapeutically effective amounts of: 
 (a) the FPT inhibitor of formula 1.0; and  
 (b) Genasense.  
 
     
     
         56 . The method of  claim 1  wherein said cancer being treated is multiple myeloma and said treatment comprises the administration of therapeutically effective amounts of: 
 (a) the FPT inhibitor of formula 1.0; and  
 (b) a proteosome inhibitor.  
 
     
     
         57 . The method of  claim 1  wherein said cancer being treated is multiple myeloma and said treatment comprises the administration of therapeutically effective amounts of: 
 (a) the FPT inhibitor of formula 1.0; and  
 (b) Thalidomide or related imid.  
 
     
     
         58 . The method of  claim 57  wherein Thalidomide is administered.  
     
     
         59 . The method of  claim 46  wherein the FPT inhibitor is administered in an amount of about 50 mg to about 200 mg twice a day.  
     
     
         60 . The method of  claim 59  wherein said FPT inhibitor is administered in an amount of about 75 mg to about 125 mg twice a day.  
     
     
         61 . The method of  claim 60  wherein said FPT inhibitor is administered in an amount of about 100 mg twice a day.  
     
     
         62 . The method of  claim 47  wherein the FPT inhibitor is administered in an amount of about 50 mg to about 200 mg twice a day.  
     
     
         63 . The method of  claim 62  wherein said FPT inhibitor is administered in an amount of about 75 mg to about 125 mg twice a day.  
     
     
         64 . The method of  claim 63  wherein said FPT inhibitor is administered in an amount of about 100 mg twice a day.  
     
     
         65 . The method of  claim 49  wherein the FPT inhibitor is administered in an amount of about 50 mg to about 200 mg twice a day.  
     
     
         66 . The method of  claim 65  wherein said FPT inhibitor is administered in an amount of about 75 mg to about 125 mg twice a day.  
     
     
         67 . The method of  claim 66  wherein said FPT inhibitor is administered in an amount of about 100 mg twice a day.  
     
     
         68 . The method of  claim 51  wherein the FPT inhibitor is administered in an amount of about 50 mg to about 200 mg twice a day.  
     
     
         69 . The method of  claim 68  wherein said FPT inhibitor is administered in an amount of about 75 mg to about 125 mg twice a day.  
     
     
         70 . The method of  claim 69  wherein said FPT inhibitor is administered in an amount of about 100 mg twice a day.  
     
     
         71 . The method of  claim 54  wherein the FPT inhibitor is administered in an amount of about 50 mg to about 200 mg twice a day.  
     
     
         72 . The method of  claim 71  wherein said FPT inhibitor is administered in an amount of about 75 mg to about 125 mg twice a day.  
     
     
         73 . The method of  claim 72  wherein said FPT inhibitor is administered in an amount of about 100 mg twice a day.  
     
     
         74 . The method of  claim 55  wherein the FPT inhibitor is administered in an amount of about 50 mg to about 200 mg twice a day.  
     
     
         75 . The method of  claim 74  wherein said FPT inhibitor is administered in an amount of about 75 mg to about 125 mg twice a day.  
     
     
         76 . The method of  claim 75  wherein said FPT inhibitor is administered in an amount of about 100 mg twice a day.  
     
     
         77 . The method of  claim 56  wherein the FPT inhibitor is administered in an amount of about 50 mg to about 200 mg twice a day.  
     
     
         78 . The method of  claim 77  wherein said FPT inhibitor is administered in an amount of about 75 mg to about 125 mg twice a day.  
     
     
         79 . The method of  claim 78  wherein said FPT inhibitor is administered in an amount of about 100 mg twice a day.  
     
     
         80 . The method of  claim 58  wherein the FPT inhibitor is administered in an amount of about 50 mg to about 200 mg twice a day.  
     
     
         81 . The method of  claim 80  wherein said FPT inhibitor is administered in an amount of about 75 mg to about 125 mg twice a day.  
     
     
         82 . The method of  claim 81  wherein said FPT inhibitor is administered in an amount of about 100 mg twice a day.  
     
     
         83 . The method of  claim 1  wherein said cancer treated is squamous cell cancer of the head and neck and said treatment comprises the administration of therapeutically effective amounts of: 
 (a) the FPT inhibitor of formula 1.0; and  
 (b) at least two different antineoplastic agents selected from the group consisting of: 
 (1) taxanes;  
 (2) platinum coordinator compounds; and  
 (3) anti-tumor nucleoside derivatives.  
 
 
     
     
         84 . The method of  claim 83  wherein the FPT inhibitor is administered in an amount of about 50 mg to about 200 mg twice a day.  
     
     
         85 . The method of  claim 84  wherein said FPT inhibitor is administered in an amount of about 75 mg to about 125 mg twice a day.  
     
     
         86 . The method of  claim 85  wherein said FPT inhibitor is administered in an amount of about 100 mg twice a day.  
     
     
         87 . The method of  claim 1  wherein said cancer being treated is non small cell lung cancer and said treatment comprises the administration of therapeutically effective amounts of: 
 (a) the FPT inhibitor of formula 1.0; and  
 (b) Carboplatin; and  
 (c) Docetaxel.  
 
     
     
         88 . The method of  claim 87  wherein: 
 (1) said FPT inhibitor is administered in an amount of about 50 mg to about 200 mg twice a day;  
 (2) said Docetaxel is administered once every three weeks in an amount of about 50 to about 100 mg/m 2 ; and  
 (3) said Carboplatin is administered once every three weeks in an amount to provide an AUC of about 5 to about 8.  
 
     
     
         89 . The method of  claim 88  wherein said docetaxel is administered once every three weeks in an amount of about 75 mg/m 2  and said Carboplatin is administered once every three weeks in an amount to provide an AUC of about 6.  
     
     
         90 . The method of  claim 89  wherein said FPT inhibitor is administered in an amount of about 75 mg to about 125 mg administered twice a day.  
     
     
         91 . The method of  claim 89  wherein said FPT inhibitor is administered in an amount of about 100 mg administered twice a day.